Using Integrated Bite Case Management to estimate the burden of rabies and evaluate surveillance in Oriental Mindoro, Philippines.

Background: Despite national elimination efforts, dog-mediated rabies remains endemic in the Philippines. Free provision of post-exposure prophylaxis (PEP) through the widespread establishment of Animal Bite Treatment Centers (ABTCs) has improved accessibility; however, the resulting upsurge in PEP demand is not sustainable, and human rabies deaths continue. Dog vaccination coverage also remains inadequate, and it is unclear whether surveillance is effective. Methods: Here, we used Integrated Bite Case Management (IBCM) to collect enhanced rabies surveillance data in Oriental Mindoro Province over a 3-year period (2020-2022). Adapting a probabilistic decision tree model, we estimated the burden of rabies, evaluated surveillance performance, and analyzed the costs and benefits of current rabies prevention and control practices in the province. Results: The incidence of bite patients receiving PEP was high in Oriental Mindoro Province (1,246/100,000 persons/year), though < 3% of presenting patients were deemed high-risk for rabies exposure (24/100,000 persons/year). Using a decision tree model, we estimated that around 73.8% of probable rabies-exposed patients sought PEP (95% Prediction Interval, PrI: 59.4%-81.1%) and that routine surveillance confirmed < 2% of circulating animal rabies cases, whereas IBCM resulted in a nearly fourfold increase in case detection. Furthermore, we estimated that an average of 560 (95% PrI 217-1,090) dogs may develop rabies annually in the province, equating to 3-5 cases per 1,000 dogs per year. On average, 20 to 43 human deaths were averted by PEP each year in Oriental Mindoro at an annual cost of $582,110 USD (i.e., $51.44 USD per person) or $20,190 USD (95% PrI $11,565-79,400) per death averted. Conclusion: While current practices for PEP provisioning in the Philippines have improved access, a large proportion of people exposed to rabies (> 26%, 95% PrI 18.8%-40.1%) are still not seeking healthcare. Integrating an intersectoral surveillance system, such as IBCM, into national policy could greatly improve case detection if well implemented, with further benefits extending to guidance for PEP administration, potentially reducing unnecessary expenditure on PEP, and situational awareness to inform control of rabies through mass dog vaccination.

Whole Genome Sequencing for Rapid Characterization of Rabies Virus Using Nanopore Technology.

Genomic data can be used to track the transmission and geographic spread of infectious diseases. However, the sequencing capacity required for genomic surveillance remains limited in many low- and middle-income countries (LMICs), where dog-mediated rabies and/or rabies transmitted by wildlife such as vampire bats pose major public health and economic concerns. We present here a rapid and affordable sample-to-sequence-to-interpretation workflow using nanopore technology. Protocols for sample collection and the diagnosis of rabies are briefly described, followed by details of the optimized whole genome sequencing workflow, including primer design and optimization for multiplex polymerase chain reaction (PCR), a modified, low-cost sequencing library preparation, sequencing with live and offline base calling, genetic lineage designation, and phylogenetic analysis. Implementation of the workflow is demonstrated, and critical steps are highlighted for local deployment, such as pipeline validation, primer optimization, inclusion of negative controls, and the use of publicly available data and genomic tools (GLUE, MADDOG) for classification and placement within regional and global phylogenies. The turnaround time for the workflow is 2-3 days, and the cost ranges from $25 per sample for a 96 sample run to $80 per sample for a 12 sample run. We conclude that setting up rabies virus genomic surveillance in LMICs is feasible and can support progress toward the global goal of zero dog-mediated human rabies deaths by 2030, as well as enhanced monitoring of wildlife rabies spread. Moreover, the platform can be adapted for other pathogens, helping to build a versatile genomic capacity that contributes to epidemic and pandemic preparedness.

Lineage BA.2 dominated the Omicron SARS-CoV-2 epidemic wave in the Philippines.

The Omicron severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant led to a dramatic global epidemic wave following detection in South Africa in November 2021. The BA.1 Omicron lineage was dominant and responsible for most SARS-CoV-2 outbreaks in countries around the world during December 2021-January 2022, while other Omicron lineages, including BA.2, accounted for the minority of global isolates. Here, we describe the Omicron wave in the Philippines by analysing genomic data. Our results identify the presence of both BA.1 and BA.2 lineages in the Philippines in December 2021, before cases surged in January 2022. We infer that only the BA.2 lineage underwent sustained transmission in the country, with an estimated emergence around 18 November 2021 (95 per cent highest posterior density: 6-28 November), while despite multiple introductions, BA.1 transmission remained limited. These results suggest that the Philippines was one of the earliest areas affected by BA.2 and reiterate the importance of whole genome sequencing for monitoring outbreaks.

Rapid in-country sequencing of whole virus genomes to inform rabies elimination programmes.

Genomic surveillance is an important aspect of contemporary disease management but has yet to be used routinely to monitor endemic disease transmission and control in low- and middle-income countries. Rabies is an almost invariably fatal viral disease that causes a large public health and economic burden in Asia and Africa, despite being entirely vaccine preventable. With policy efforts now directed towards achieving a global goal of zero dog-mediated human rabies deaths by 2030, establishing effective surveillance tools is critical. Genomic data can provide important and unique insights into rabies spread and persistence that can direct control efforts. However, capacity for genomic research in low- and middle-income countries is held back by limited laboratory infrastructure, cost, supply chains and other logistical challenges. Here we present and validate an end-to-end workflow to facilitate affordable whole genome sequencing for rabies surveillance utilising nanopore technology. We used this workflow in Kenya, Tanzania and the Philippines to generate rabies virus genomes in two to three days, reducing costs to approximately £60 per genome. This is over half the cost of metagenomic sequencing previously conducted for Tanzanian samples, which involved exporting samples to the UK and a three- to six-month lag time. Ongoing optimization of workflows are likely to reduce these costs further. We also present tools to support routine whole genome sequencing and interpretation for genomic surveillance. Moreover, combined with training workshops to empower scientists in-country, we show that local sequencing capacity can be readily established and sustainable, negating the common misperception that cutting-edge genomic research can only be conducted in high resource laboratories. More generally, we argue that the capacity to harness genomic data is a game-changer for endemic disease surveillance and should precipitate a new wave of researchers from low- and middle-income countries.